Aldehydes strecker-type reaction

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

The Strecker amino acid synthesis, which involves treatment of aldehydes with ammonia and hydrogen cyanide (or equivalents) followed by hydrolysis of the intermediate a-amino nitriles to provide a-amino acids (Scheme 1), was first reported in 1850 [1], This method has been applied on an industrial scale toward the synthesis of racemic a-amino acids, but more recently interest in nonproteinogenic a-amino acids in a variety of scientific disciplines has prompted intense activity in the asymmetric syntheses of a-amino acids [2]. The catalytic asymmetric Strecker-type reaction offers one of the most direct and viable methods for the asymmetric synthesis of a-amino acid derivatives. It is the purpose of this Highlight to disclose recent developments in this emerging field of importance. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Several examples of the Strecker-type reaction were tested. For all the compounds investigated, including aromatic, aliphatic, heterocyclic, and aj3-unsaturated aldehydes, the reactions proceeded smoothly to afford the corresponding a-amino nitriles in high yield. The adducts, a-(A-benzhydryl)amino nitriles, were readily converted to a-amino acids [78], and Strecker-type reactions using other amines such as aniline and benzylamine also proceeded smoothly to afford the corresponding adducts in high yields. 

Aromatic and aliphatic aldehydes in the presence of dialkylamines and an equivalent of acid such as hydrochloric, perchloric or p-toluenesulfonic acid give iminium salts, which add cyanide ion to form a-(dialkylamino)nitriles. An alternative preparation involves the reaction of the aldehyde with dialkylamines in the presence of acetone-cyanohydrin, a-(A, -dialkylamino)isobutyronitiiles, diethyl phosphorocyanidate or TMS-CN. Another route to a-aminonitrile starts with an aldehyde, the salt of an amine and KCN in organic solvents under solid-liquid two-phase conditions by combined use of alumina and ultrasound. Chiral a-aminonitriles were prepared by Strecker-type reactions, cyano-silylation of Schiffs bases, amination of a-siloxynitriles or from an A -cyanomethyl-l,3-oxazolidine synthon. Reaction of tertiary amines with CIO2 in the presence of 5.1 mol equiv. of aqueous NaCN as an external nucleophile affords a-aminonitrile. °... 

Hofmann, T, Mlinch, P, Schieberle, P. Quantitative model studies on the formation of aroma-active aldehydes and acids by Strecker-type reactions. J. Agric. Food Chem. 2000, 48, 434-440. 

Cyanosilylation of imines (Strecker-type reaction) is efficiently promoted by conventional Lewis acids such as ZnX2, AlCl , and TiCLj [604]. Kobayashi et al. recently disclosed that Yb(OTf)3 has high catalytic activity in this cyanosilylation (Scheme 10.237) [622]. In the competitive reaction of aldehydes and the corresponding imines with TMSCN, Yb(OTf)3 activates imines to give only a-aminoni-... 

Thus, Strecker-type reactions of aldehydes, amines, and Bu3SnCN were successfully performed using Sc(OTf)3 as a catalyst. The reactions proceeded smoothly in both organic and aqueous solutions to afford a-amino nitriles in high yields. It is noted that the experimental procedure is very simple just mixing the three components and Sc(OTf)3 in an appropriate solvent at room temperature. Moreover, complete recovery of the tin materials in these reactions has been achieved. While many useful tin reagents have been... 

S. Kobayashi, T. Busujima, S. Nagayama, Chem. Commun. 1998, 981-982. Scandium triflate-catalyzed Strecker-type reactions of aldehydes, amines and tributyltin cyanide in both organic and aqueous solutions. Achievement of complete recovery of the tin compounds toward environmentally-friendly chemical processes. 

The Strecker reaction starting from an aldehyde, ammonia and a cyanide source is an efficient method for the preparation of a-amino acids and their derivatives. A popular version for asymmetric purposes is based on the use of preformed imines and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst. An intense investigation of the asymmetric Strecker-type reaction has continued over many years, due to the importance of a-amino acid building blocks in medicinal chemistry. Interestingly, a number... 

Kobayashi et al. reported that Strecker-type reaction of aldehydes, amines, and TMSCN proceeded efficiently with Yb(OTf)3 as catalyst [30]. Both aliphatic and aromatic aldehydes afforded the corresponding a-aminonitrile in high yield... 

Addition to Carbonyls, Imines (Strecker-type Reactions), and Heteroaromatic Rings (Reissert-type Reactions). Cyanohydrin trimethylsilyl ethers are of significant synthetic interest as they can be transformed into a variety of multifunctional intermediates. Aldehydes and ketones can be enantioselectively converted to cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of a Lewis acid and a chiral ligand. Enantioselective and/or diastereoselective formation of cyanohydrins and their derivatives has been reported and most of these reactions involve chiral ligands and metal catalysts containing Ti (eq 24), Sm (eq 25), and A1 (eq 26). ... 

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

Amines via condensations. Tryptophan derivatives are obtained by reaction of indoles with A-substituted aziridinecarboxylic esters at 0° or room temperature. Stoichiometric amount of Sc(OTf)3 is required. By SclOTfjj catalysis the Strecker-type synthesis from aldehydes, amines, and BujSnCN can be carried out either in organic solvents or in water. Pictet-Spengler reaction is directly accomplished using acetals. ... 

Kobayashi et al. disclosed reversed chemoselectivity of lanthanide Lewis acid over conventional Lewis acid in cyanation reaction. The comparitive reaction was performed with equimolar mixture of aldehydes, imines, and TMSCN, affording Strecker-type product exclusively with 20mol% of Yb(OTf)3 [10]. In sharp contrast, SnCU required more than a stoichiometric amount of reagent and gave cyanohydrin preferentially (Table 13.15). 

Monoaminomonocarboxylic a-amino acids with a primary amino group produce sensory active aldehydes called Strecker aldehydes. Strecker degradation of P-amino acids yields alkan-2-ones known as methylketones (see Section 8.2.4.1.2). By analogy, alkane-3-ones (ethylketones) are formed from y-amino acids. The general reaction is schematically indicated in Figure 2.43. The reaction mechanism, however, varies considerably depending on the type of oxidant and amino acid. 2-Imino acids and 2-oxoacids can in some cases apparently form as intermediates, analogous to enzymatically catalysed transamination and oxidative deamination of amino acids (see Section 2.5.1.3.2). Some Strecker aldehydes readily decompose, such as methional, or yield cyclic products, such as 5-aminopentanal, which dehydrates to 2,3,4,5-tetrahydropyridine. 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

Also acetic acid may arise from a reaction of this type. Most important compounds of this pathway are pyruvic aldehyde, diacetyl, hydro-oxyacetone and hydroxydiacetyl which can easily react with amino acids. The Strecker degradation is a reaction where the amino acid is de-carboxylated and loses its amino group. Reaction products are the Strecker aldehyde and - as an intermediate - an aminoketone which forms a pyrazine by dimerization. This pathway is considered to be most important for the origin of pyrazines in thermal aromas. However, only limited knowledge is available about the fate of the Strecker aldehydes. As we will demonstrate they are very reactive. 

Tressl et al7r J1 designated the linear polymers as Type I and the branched ones as Type II. In most melanoidins, they would represent domains (or substructures), unsubstituted pyrroles and Strecker aldehydes, for example, being integrated into the melanoidin backbone, giving a complex macromolecular structure overall. Tressl et aV1 consider the oligomerisation/polycondensation reactions described as the only experimentally established pathways by which simple Maillard products generated from hexoses and pentoses are easily and irreversibly converted into macromolecules. 

Each elementary step is reversible. At fist glance, this type of reaction should afford a complex reaction mixture of product, all possible intermediates, and starting materials. However, if the desired adduct is thermodynamically more stable than any other intermediates, the reaction can still be high yielding and become synthetically useful. The Strecker reaction is a typical example. Although the condensation of an aldehyde, an amine leading to iminium intermediate and subsequent nucleophilic addition of cyanide are in principle reversible under aqueous acidic conditions. The a-aminonitrile can be obtained in high yield under appropriate conditions. 

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